European Medicines Agency Recommends Restricting Use of Pandemrix

In persons under 20 years of age Pandemrix to be used only in
the absence of seasonal trivalent influenza vaccines, following
link to very rare cases of narcolepsy in young people. Overall
benefit-risk remains positive.

LONDON, July 21, 2011 - Finalising its review of Pandemrix and
narcolepsy the European Medicines Agency’s Committee for
Medicinal Products for Human Use (CHMP) recommended that in persons
under 20 years of age Pandemrix may only be used if the recommended
seasonal trivalent influenza vaccine is not available and if
immunisation against H1N1 is still needed (e.g. in persons at risk
of the complications of infection). The CHMP confirmed that overall
the benefit-risk balance of Pandemrix remains positive.

The review of Pandemrix was initiated to investigate a possible
link between Pandemrix vaccination and narcolepsy, following an
increased number of reported cases of narcolepsy among children and
adolescents in Finland and Sweden. The reported cases of narcolepsy
occurred following the H1N1 pandemic vaccination campaign in late
2009 and early 2010. The current review has been conducted in the
context of seasonal use.

The CHMP considered all available data on the possible
association between Pandemrix and narcolepsy and the impact on the
overall benefit-risk balance of Pandemrix. These included the
results of epidemiological studies carried out in Finland and
Sweden, analysis of safety surveillance data performed in several
Member States and case reports from across the European Union (EU).
They also included the preliminary results of an epidemiological
study of narcolepsy and pandemic vaccines in eight EU Member
States, coordinated by the European Centre for Disease Prevention
and Control (ECDC) through a network of research and public health
institutions (VAESCO).

The CHMP also took advice from a specially convened meeting of
experts in fields such as paediatric neurology, vaccinology,
immunology, sleep disorders, infectious diseases, epidemiology, as
well as experts from Health Canada, the World Health Organization
(WHO) and the ECDC, to consider the latest available data regarding
the possible link between Pandemrix and narcolepsy.

The CHMP considered that the epidemiological studies relating to
Pandemrix in Finland and Sweden were well designed and the results
show an association between Pandemrix vaccination and narcolepsy in
children and adolescents in those countries. The results indicate a
six- to 13-fold increased risk of narcolepsy with or without
cataplexy in vaccinated as compared with unvaccinated children and
adolescents, corresponding to about an additional three to seven
cases in every 100,000 vaccinated subjects. This risk increase has
not been found in adults (older than 20 years). A similar risk has
not been confirmed but cannot be ruled out in other countries.

The Committee noted that the vaccine is likely to have
interacted with genetic or environmental factors which might raise
the risk of narcolepsy, and that other factors may have contributed
to the results. There are several initiatives being developed
across the EU to further investigate this association.

The CHMP noted that similar epidemiological studies have not
been completed in other countries. The preliminary results of the
VAESCO study confirmed the signal in Finland. Results are still
preliminary and do not allow conclusions in other countries (where
vaccination coverage with Pandemrix was lower), but the final
results of the VAESCO study are still awaited.

Exposure to specific infectious diseases (including H1N1) at
different ages, particularly upper respiratory infections, may have
contributed to the observations in the Nordic area. The CHMP
considered that it would be helpful if ongoing epidemiological
studies seek to address this question.

The CHMP stressed that further research is necessary.

The marketing authorisation holder for Pandemrix,
GlaxoSmithKline, is carrying out a retrospective cohort study in
Canada, where an equivalent H1N1 vaccine (Arepanrix) was widely
used. The company is required to carry out non-clinical and
clinical studies in order to further explore the association
between Pandemrix vaccination and narcolepsy.

Notes

Narcolepsy is a rare sleep disorder that causes a person to fall
asleep suddenly and unexpectedly. Its precise cause is unknown, but
it is generally considered to be triggered by a combination of
genetic and environmental factors. Narcolepsy occurs naturally at a
rate of around 1 case per 100,000 people every year.
Pandemrix, an (H1N1)v influenza vaccine, has been authorised since
September 2009, and was used during the 2009 H1N1 influenza
pandemic in at least 30.8 million Europeans.
The H1N1 influenza strain continues to be the predominant strain in
this season.
The review of Pandemrix and narcolepsy was initiated at the request
of the European Commission under Article 20 of Regulation (EC) No
726/2004, on 27 August 2010, following an increased number of
reports on narcolepsy in Finland and Sweden.